The PIO are pretty great and not niche. Almost any embedded application needs mixed signal interfaces. You could say embedded applications are niche, but not that embedded applications needing mixed signal interfaces.
A serious warning: read the RP2350 errata carefully. You may be better off buying old 2040 inventory.
> read the RP2350 errata carefully
Even the latest rev? Can you elaborate a bit?
Mixed signal means analog and digital
RP2350 adds secure boot and encrypted boot. I am working on a little hardware device for a CTF and selected it as my MCU so participants can't just dump the flash to grab the flags.